Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study
Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the h...
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| Veröffentlicht in: | PloS one 2016-04, Vol.11 (4), p.e0153274-e0153274 |
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| creator | Audirac-Chalifour, Astride Torres-Poveda, Kirvis Bahena-Román, Margarita Téllez-Sosa, Juan Martínez-Barnetche, Jesús Cortina-Ceballos, Bernardo López-Estrada, Guillermina Delgado-Romero, Karina Burguete-García, Ana I Cantú, David García-Carrancá, Alejandro Madrid-Marina, Vicente |
| description | Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p |
| doi_str_mv | 10.1371/journal.pone.0153274 |
| format | Article |
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Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0153274</identifier><identifier>PMID: 27115350</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Analysis ; Bacteria ; Biology and Life Sciences ; Cancer ; Carcinoma, Squamous Cell - immunology ; Carcinoma, Squamous Cell - microbiology ; Carcinoma, Squamous Cell - pathology ; Cervical cancer ; Cervix ; Cross-Sectional Studies ; Cytokines ; Cytokines - genetics ; Cytology ; Diagnosis ; Ecology and Environmental Sciences ; Female ; Fusobacterium ; Gene expression ; Health risks ; Human papillomavirus ; Humans ; Immunosuppression ; Interferon ; Interferon-gamma - genetics ; Interleukin 10 ; Interleukin 4 ; Interleukin 6 ; Interleukin-10 - genetics ; Interleukin-4 - genetics ; Interleukin-6 - genetics ; Lesions ; Medicine and Health Sciences ; Microbiomes ; Microbiota ; Middle Aged ; Neoplasm Staging ; Next-generation sequencing ; Papillomavirus infections ; Research and Analysis Methods ; Risk factors ; RNA, Messenger - genetics ; RNA, Neoplasm - genetics ; rRNA 16S ; Squamous Intraepithelial Lesions of the Cervix - immunology ; Squamous Intraepithelial Lesions of the Cervix - microbiology ; Squamous Intraepithelial Lesions of the Cervix - pathology ; Transcriptome ; Transforming Growth Factor beta1 - genetics ; Transforming growth factor-b1 ; Tumor Necrosis Factor-alpha - genetics ; Tumor necrosis factor-α ; Uterine Cervical Neoplasms - immunology ; Uterine Cervical Neoplasms - microbiology ; Uterine Cervical Neoplasms - pathology ; Vagina ; γ-Interferon</subject><ispartof>PloS one, 2016-04, Vol.11 (4), p.e0153274-e0153274</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Audirac-Chalifour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Audirac-Chalifour et al 2016 Audirac-Chalifour et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c791t-9dddc63f7bf247979506758c9865aba2aa80458471eab7d82c5de0c1ecf605f53</citedby><cites>FETCH-LOGICAL-c791t-9dddc63f7bf247979506758c9865aba2aa80458471eab7d82c5de0c1ecf605f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846060/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846060/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27115350$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Audirac-Chalifour, Astride</creatorcontrib><creatorcontrib>Torres-Poveda, Kirvis</creatorcontrib><creatorcontrib>Bahena-Román, Margarita</creatorcontrib><creatorcontrib>Téllez-Sosa, Juan</creatorcontrib><creatorcontrib>Martínez-Barnetche, Jesús</creatorcontrib><creatorcontrib>Cortina-Ceballos, Bernardo</creatorcontrib><creatorcontrib>López-Estrada, Guillermina</creatorcontrib><creatorcontrib>Delgado-Romero, Karina</creatorcontrib><creatorcontrib>Burguete-García, Ana I</creatorcontrib><creatorcontrib>Cantú, David</creatorcontrib><creatorcontrib>García-Carrancá, Alejandro</creatorcontrib><creatorcontrib>Madrid-Marina, Vicente</creatorcontrib><title>Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings.</description><subject>Adult</subject><subject>Analysis</subject><subject>Bacteria</subject><subject>Biology and Life Sciences</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - immunology</subject><subject>Carcinoma, Squamous Cell - microbiology</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Cross-Sectional Studies</subject><subject>Cytokines</subject><subject>Cytokines - genetics</subject><subject>Cytology</subject><subject>Diagnosis</subject><subject>Ecology and Environmental Sciences</subject><subject>Female</subject><subject>Fusobacterium</subject><subject>Gene expression</subject><subject>Health risks</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>Immunosuppression</subject><subject>Interferon</subject><subject>Interferon-gamma - genetics</subject><subject>Interleukin 10</subject><subject>Interleukin 4</subject><subject>Interleukin 6</subject><subject>Interleukin-10 - genetics</subject><subject>Interleukin-4 - genetics</subject><subject>Interleukin-6 - genetics</subject><subject>Lesions</subject><subject>Medicine and Health Sciences</subject><subject>Microbiomes</subject><subject>Microbiota</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Next-generation sequencing</subject><subject>Papillomavirus infections</subject><subject>Research and Analysis Methods</subject><subject>Risk factors</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Neoplasm - genetics</subject><subject>rRNA 16S</subject><subject>Squamous Intraepithelial Lesions of the Cervix - immunology</subject><subject>Squamous Intraepithelial Lesions of the Cervix - microbiology</subject><subject>Squamous Intraepithelial Lesions of the Cervix - pathology</subject><subject>Transcriptome</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Transforming growth factor-b1</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Tumor necrosis factor-α</subject><subject>Uterine Cervical Neoplasms - immunology</subject><subject>Uterine Cervical Neoplasms - microbiology</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Vagina</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBEQkJw0WIn_goXSFXFR6WhTQx2hWSdOE7r4sbFTib673FoVjVoF5MvbNnP-_r4-JwkeY7RFOccv1u7zjdgp1vX6CnCNM84eZCc4iLPJixD-cOj9UnyJIQ1QjQXjD1OTjKOo4Ci0-TnXPsbo8CmX43yrjRuo1NoqnS-a90v0-j00rva2LjZptfgjetCetXCUofU1elBPYdGaf8-naWXxro2Il21e5o8qsEG_WyYz5Ifnz5-n3-ZnF98Xsxn5xPFC9xOiqqqFMtrXtYZ4QUvKGKcClUIRqGEDEAgQgXhWEPJK5EpWmmksFY1Q7Sm-Vnycu-7tS7IITFBYi4IYYjznljsicrBWm692YDfSQdG_ttwfinBt0ZZLQWtuKAlV5wRUigEiBOW0VoD57wAEb0-DLd15UZXSjetBzsyHZ80ZiWX7kYSEaNhKBq8GQy8-93p0MqNCUpbC42O6Y1xF_FmigS5BypohglGeURf_YfenYiBWkJ8q2lqF0NUvamcEZqTjNGsj3B6BxVHpTdGxYLrK2IseDsSRKbVf9oldCHIxdW3-7MX12P29RG70mDbVXC2a41rwhgkezAWcQhe14f_wEj2_XKbDdn3ixz6JcpeHP_lQXTbIPlfCcwNiA</recordid><startdate>20160426</startdate><enddate>20160426</enddate><creator>Audirac-Chalifour, Astride</creator><creator>Torres-Poveda, Kirvis</creator><creator>Bahena-Román, Margarita</creator><creator>Téllez-Sosa, Juan</creator><creator>Martínez-Barnetche, Jesús</creator><creator>Cortina-Ceballos, Bernardo</creator><creator>López-Estrada, Guillermina</creator><creator>Delgado-Romero, Karina</creator><creator>Burguete-García, Ana I</creator><creator>Cantú, David</creator><creator>García-Carrancá, Alejandro</creator><creator>Madrid-Marina, Vicente</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160426</creationdate><title>Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study</title><author>Audirac-Chalifour, Astride ; Torres-Poveda, Kirvis ; Bahena-Román, Margarita ; Téllez-Sosa, Juan ; Martínez-Barnetche, Jesús ; Cortina-Ceballos, Bernardo ; López-Estrada, Guillermina ; Delgado-Romero, Karina ; Burguete-García, Ana I ; Cantú, David ; García-Carrancá, Alejandro ; Madrid-Marina, Vicente</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c791t-9dddc63f7bf247979506758c9865aba2aa80458471eab7d82c5de0c1ecf605f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Analysis</topic><topic>Bacteria</topic><topic>Biology and Life Sciences</topic><topic>Cancer</topic><topic>Carcinoma, Squamous Cell - immunology</topic><topic>Carcinoma, Squamous Cell - microbiology</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Cross-Sectional Studies</topic><topic>Cytokines</topic><topic>Cytokines - genetics</topic><topic>Cytology</topic><topic>Diagnosis</topic><topic>Ecology and Environmental Sciences</topic><topic>Female</topic><topic>Fusobacterium</topic><topic>Gene expression</topic><topic>Health risks</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>Immunosuppression</topic><topic>Interferon</topic><topic>Interferon-gamma - genetics</topic><topic>Interleukin 10</topic><topic>Interleukin 4</topic><topic>Interleukin 6</topic><topic>Interleukin-10 - genetics</topic><topic>Interleukin-4 - genetics</topic><topic>Interleukin-6 - genetics</topic><topic>Lesions</topic><topic>Medicine and Health Sciences</topic><topic>Microbiomes</topic><topic>Microbiota</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Next-generation sequencing</topic><topic>Papillomavirus infections</topic><topic>Research and Analysis Methods</topic><topic>Risk factors</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Neoplasm - genetics</topic><topic>rRNA 16S</topic><topic>Squamous Intraepithelial Lesions of the Cervix - immunology</topic><topic>Squamous Intraepithelial Lesions of the Cervix - microbiology</topic><topic>Squamous Intraepithelial Lesions of the Cervix - pathology</topic><topic>Transcriptome</topic><topic>Transforming Growth Factor beta1 - genetics</topic><topic>Transforming growth factor-b1</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><topic>Tumor necrosis factor-α</topic><topic>Uterine Cervical Neoplasms - immunology</topic><topic>Uterine Cervical Neoplasms - microbiology</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Vagina</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Audirac-Chalifour, Astride</creatorcontrib><creatorcontrib>Torres-Poveda, Kirvis</creatorcontrib><creatorcontrib>Bahena-Román, Margarita</creatorcontrib><creatorcontrib>Téllez-Sosa, Juan</creatorcontrib><creatorcontrib>Martínez-Barnetche, Jesús</creatorcontrib><creatorcontrib>Cortina-Ceballos, Bernardo</creatorcontrib><creatorcontrib>López-Estrada, Guillermina</creatorcontrib><creatorcontrib>Delgado-Romero, Karina</creatorcontrib><creatorcontrib>Burguete-García, Ana I</creatorcontrib><creatorcontrib>Cantú, David</creatorcontrib><creatorcontrib>García-Carrancá, Alejandro</creatorcontrib><creatorcontrib>Madrid-Marina, Vicente</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale_Opposing Viewpoints In Context</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Audirac-Chalifour, Astride</au><au>Torres-Poveda, Kirvis</au><au>Bahena-Román, Margarita</au><au>Téllez-Sosa, Juan</au><au>Martínez-Barnetche, Jesús</au><au>Cortina-Ceballos, Bernardo</au><au>López-Estrada, Guillermina</au><au>Delgado-Romero, Karina</au><au>Burguete-García, Ana I</au><au>Cantú, David</au><au>García-Carrancá, Alejandro</au><au>Madrid-Marina, Vicente</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-04-26</date><risdate>2016</risdate><volume>11</volume><issue>4</issue><spage>e0153274</spage><epage>e0153274</epage><pages>e0153274-e0153274</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27115350</pmid><doi>10.1371/journal.pone.0153274</doi><tpages>e0153274</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-04, Vol.11 (4), p.e0153274-e0153274 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1784460775 |
| source | Electronic Journals Library; MEDLINE; DOAJ Directory of Open Access Journals; PLoS_OA刊; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Analysis Bacteria Biology and Life Sciences Cancer Carcinoma, Squamous Cell - immunology Carcinoma, Squamous Cell - microbiology Carcinoma, Squamous Cell - pathology Cervical cancer Cervix Cross-Sectional Studies Cytokines Cytokines - genetics Cytology Diagnosis Ecology and Environmental Sciences Female Fusobacterium Gene expression Health risks Human papillomavirus Humans Immunosuppression Interferon Interferon-gamma - genetics Interleukin 10 Interleukin 4 Interleukin 6 Interleukin-10 - genetics Interleukin-4 - genetics Interleukin-6 - genetics Lesions Medicine and Health Sciences Microbiomes Microbiota Middle Aged Neoplasm Staging Next-generation sequencing Papillomavirus infections Research and Analysis Methods Risk factors RNA, Messenger - genetics RNA, Neoplasm - genetics rRNA 16S Squamous Intraepithelial Lesions of the Cervix - immunology Squamous Intraepithelial Lesions of the Cervix - microbiology Squamous Intraepithelial Lesions of the Cervix - pathology Transcriptome Transforming Growth Factor beta1 - genetics Transforming growth factor-b1 Tumor Necrosis Factor-alpha - genetics Tumor necrosis factor-α Uterine Cervical Neoplasms - immunology Uterine Cervical Neoplasms - microbiology Uterine Cervical Neoplasms - pathology Vagina γ-Interferon |
| title | Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study |
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